The cornea is the clear window through which the eye sees. The studies in this grant proposal are designed to answer questions concerning the cells of the cornea, how they respond to preservation, transplantation, disease, and topical drug therapy, as well as how they protect themselves from ambient ultraviolet light. Most of the studies are concerned with human corneas. Human corneal cells will be photographed and analyzed in vivo in transplanted corneas, in corneas with keratoconus and Fuchs' dystrophy, and in corneas after long-term contact lens wear or topical ocular hypertensive therapy. A tandem scanning confocal microscope will be used to image the stromal keratocytes in these conditions and determine their number. The instrument will also determine epithelial thickness and stromal light reflectivity. A endothelial specular microscope will be used to image and count the endothelial cells. A unique series of 500 consecutive patients with corneal transplants will be examined at 5-year intervals 15, 20, and 25 years after transplantation in order to learn the long-term course of these operations and the importance of various preoperative and surgical factors. Apoptosis (programmed cell death) in newly transplanted human corneas and human corneal cryopreservation will be studied in a xenograft model. Finally, the high concentrations of ascorbate (vitamin C) in the corneal epithelium will be investigated in humans, guinea pigs, and rabbits as a possible mechanism by which the ocular cells are protected from the damaging effects of ultraviolet light.